The proposed research project will investigate means for inducing immunity to lower respiratory tract disease caused by nontypable Hemophilus influenza (NTHI). This bacterial organism is an important cause of both tracheobronchitis and pneumonia in elderly or debilitated persons, and especially affects people with chronic obstructive pulmonary disease. Selected surface antigens of this organism will be evaluated for their vaccinogenic potential. An animal model system will be utilized to measure the effects of active immunization regimens on pulmonary clearance rates. Recombinant DNA techniques will be used to clone the genes encoding the P2 major outer membrane protein and the P6 lipoproteins of NTHI. The resultant recombinant proteins will be purified from E. coli in a form free from contamination with other NTHI antigens. These purified proteins will be studied for their ability to induce pulmonary immunity to NTHI. A previously undescribed surface antigen of NTHI, which has been shown to be a target for monoclonal antibodies which enhance pulmonary clearance of NTHI, will also be purified and evaluated for its vaccinogenic potential. Finally, monoclonal antibody technology will be used in conjunction with the animal model system to investigate the role of antibody isotype in immune defense in the lung.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
Project #
Application #
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Texas Sw Medical Center Dallas
Schools of Medicine
United States
Zip Code
Sanders, J D; Cope, L D; Hansen, E J (1994) Identification of a locus involved in the utilization of iron by Haemophilus influenzae. Infect Immun 62:4515-25
Sanders, J D; Cope, L D; Jarosik, G P et al. (1993) Reconstitution of a porin-deficient mutant of Haemophilus influenzae type b with a porin gene from nontypeable H. influenzae. Infect Immun 61:3966-75
Hansen, E J; Toews, G B (1992) Animal models for the study of noninvasive Haemophilus influenzae disease: pulmonary clearance systems. J Infect Dis 165 Suppl 1:S185-7
Toews, G B; Hansen, E J; Strieter, R M (1990) Pulmonary host defenses and oropharyngeal pathogens. Am J Med 88:20S-24S
McGehee, J L; Radolf, J D; Toews, G B et al. (1989) Effect of primary immunization on pulmonary clearance of nontypable Haemophilus influenzae. Am J Respir Cell Mol Biol 1:201-10
Hansen, E J; Toews, G B (1989) Pulmonary clearance of nontypable Haemophilus influenzae. Pediatr Infect Dis J 8:S69-72
Hansen, E J; Hart, D A; McGehee, J L et al. (1988) Immune enhancement of pulmonary clearance of nontypable Haemophilus influenzae. Infect Immun 56:182-90
Patrick, C C; Kimura, A; Jackson, M A et al. (1987) Antigenic characterization of the oligosaccharide portion of the lipooligosaccharide of nontypable Haemophilus influenzae. Infect Immun 55:2902-11